Polygenic Scores and Onset of Major Mood or Psychotic Disorders Among Offspring of Affected Parents

被引：10

作者：

Zwicker, Alyson ^{[1
,3
,4
]}

Fullerton, Janice M. ^{[5
,6
]}

Mullins, Niamh ^{[7
,8
]}

Rice, Frances ^{[9
,10
]}

Hafeman, Danella M. ^{[11
]}

van Haren, Neeltje E. M. ^{[12
,13
]}

Setiaman, Nikita ^{[12
,13
]}

Merranko, John A. ^{[11
]}

Goldstein, Benjamin I. ^{[14
]}

Ferrera, Alessandra G. ^{[15
]}

Stapp, Emma K. ^{[17
]}

de la Serna, Elena ^{[18
,19
,20
]}

Moreno, Dolores ^{[18
,21
]}

Sugranyes, Gisela ^{[18
,19
,20
]}

Herrero, Sergio Mas ^{[22
]}

Roberts, Gloria ^{[23
]}

Toma, Claudio ^{[5
,6
,24
]}

Schofield, Peter R. ^{[5
,6
]}

Edenberg, Howard J. ^{[25
]}

Wilcox, Holly C. ^{[26
]}

McInnis, Melvin G. ^{[27
]}

Powell, Victoria ^{[9
,10
]}

Propper, Lukas ^{[1
,28
]}

Denovan-Wright, Eileen ^{[1
,2
]}

Rouleau, Guy ^{[29
,30
]}

Castro-Fornieles, Josefina ^{[19
,20
,31
]}

Hillegers, Manon H. J. ^{[12
,13
]}

Birmaher, Boris ^{[11
]}

Thapar, Anita ^{[9
,10
]}

Mitchell, Philip B. ^{[23
]}

Lewis, Cathryn M. ^{[32
]}

Alda, Martin ^{[1
,3
]}

Nurnberger, John I. ^{[15
,16
]}

Uher, Rudolf ^{[1
,3
]}

机构：

[1] Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada

[2] Dalhousie Univ, Dept Pharmacol, Halifax, NS, Canada

[3] Nova Scotia Hlth, Halifax, NS, Canada

[4] Dalhousie Med New Brunswick, St John, NB, Canada

[5] Neurosci Res Australia, Randwick, NSW, Australia

[6] Univ New South Wales, Sch Med Sci, Kensington, Australia

[7] Icahn Sch Med atMount Sinai, Dept Genet & Genom Sci, New York, NY USA

[8] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY USA

[9] Cardiff Univ, Wolfson Ctr Young Peoples Mental Hlth, Div Psychol Med & Clin Neurosci, Sect Child & Adolescent Psychiat, Cardiff, Wales

[10] Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Div Psychol Med & Clin Neurosci, Cardiff, Wales

[11] Univ Pittsburgh, Western Psychiat Hosp, Sch Med, Pittsburgh, PA USA

[12] Erasmus Univ, Sophia Childrens Hosp, Dept Child & Adolescent Psychiat Psychol, Med Ctr, Rotterdam, Netherlands

[13] Univ Med Ctr Utrecht Brain Ctr, Dept Psychiat, Utrecht, Netherlands

[14] Univ Toronto, Ctr Addict & Mental Hlth, Fac Med, Toronto, ON, Canada

[15] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN USA

[16] Indiana Univ Sch Med, Stark Neurosci Res Inst, Indianapolis, IN USA

[17] NIMH, Bethesda, MD USA

[18] Inst Invest Biomed Agusti Pi i Sunyer IDIBAPS, Barcelona, Spain

[19] Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain

[20] Hosp Clin Barcelona, Inst Neurosci, Dept Child & Adolescent Psychiat & Psychol, Barcelona, Spain

[21] Hosp Gen Univ Gregorio Maranon, Child & Adolescent Psychiat Dept, Madrid, Spain

[22] Univ Barcelona, Dept Psychiat, Barcelona, Spain

[23] Univ New South Wales, Sch Psychiat, Randwick, NSW, Australia

[24] Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, CSIC, Madrid, Spain

[25] Indiana Univ, Dept Biochem & Mol Biol, Indianapolis, IN USA

[26] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA

[27] Univ Michigan, Dept Psychiat, Ann Arbor, MI USA

[28] IWK Hlth Ctr, Halifax, NS, Canada

[29] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada

[30] McGill Univ, Dept Neurol, Montreal, PQ, Canada

[31] Univ Barcelona, Dept Med cine, Barcelona, Spain

[32] Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Ctr, London, England

来源：

AMERICAN JOURNAL OF PSYCHIATRY | 2023年 / 180卷 / 04期

基金：

澳大利亚国家健康与医学研究理事会; 加拿大健康研究院; 英国医学研究理事会;

关键词：

BIPOLAR DISORDER; RISK; SCHIZOPHRENIA; ADOLESCENT; PSYCHOPATHOLOGY; RELIABILITY; DEPRESSION; VARIANTS; SYMPTOMS; CHILDREN;

D O I：

10.1176/appi.ajp.20220476

中图分类号：

R749 [精神病学];

学科分类号：

100205 ;

摘要：

Objective: Family history is an established risk factor for mental illness. The authors sought to investigate whether polygenic scores (PGSs) can complement family history to improve identification of risk for major mood and psychotic disorders. Methods: Eight cohorts were combined to create a sample of 1,884 participants ages 2-36 years, including 1,339 off-spring of parents with mood or psychotic disorders, who were prospectively assessed with diagnostic interviews over an average of 5.1 years. PGSs were constructed for depres-sion, bipolar disorder, anxiety, attention deficit hyperactivity disorder (ADHD), schizophrenia, neuroticism, subjective well-being, p factor, and height (as a negative control). Cox regression was used to test associations between PGSs, family history of major mental illness, and onsets of major mood and psychotic disorders. Results: There were 435 onsets of major mood and psy-chotic disorders across follow-up. PGSs for neuroticism (hazard ratio=1.23, 95% CI=1.12-1.36), schizophrenia (hazard ratio=1.15, 95% CI=1.04-1.26), depression (hazard ratio=1.11, 95% CI=1.01-1.22), ADHD (hazard ratio=1.10, 95% CI=1.00-1.21), subjective well-being (hazard ra-tio=0.90, 95% CI=0.82-0.99), and p factor (hazard ra-tio=1.14, 95% CI=1.04-1.26) were associated with onsets. After controlling for family history, neuroticism PGS remained significantly positively associated (hazard ratio=1.19, 95% CI=1.08-1.31) and subjective well-being PGS remained significantly negatively associated (hazard ratio=0.89, 95% CI=0.81-0.98) with onsets. Conclusions: Neuroticism and subjective well-being PGSs capture risk of major mood and psychotic disorders that is independent of family history, whereas PGSs for psychiatric illness provide limited predictive power when family history is known. Neuroticism and subjective well-being PGSs may complement family history in the early identification of persons at elevated risk. Am J Psychiatry 2023; 180:285-293; doi:10.1176/appi.ajp.20220476

引用

页码：285 / 293

页数：9

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